Trifluoroacetic acid → HCID 67432651, compound

HRID 410635Notes

Reaction equation

HRID 410635 reaction equation
[OH:1][CH2:2][C:3]([O:5]C)=[O:4].Cl[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]2[CH:16]=[C:17]([C:22]3[S:26][C:25]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[N:24][CH:23]=3)[CH:18]=[C:19]([CH3:21])[CH:20]=2)[N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)C(O)=O>>[CH3:21][C:19]1[CH:20]=[C:15]([NH:14][C:10]2[N:9]=[C:8]([O:1][CH2:2][C:3]([OH:5])=[O:4])[CH:13]=[CH:12][N:11]=2)[CH:16]=[C:17]([C:22]2[S:26][C:25]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[N:24][CH:23]=2)[CH:18]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 66774Methyl GlycolateHCID 58456107HCID 58456107, compound

Product 1

HCID 67432651HCID 67432651, compoundYield 15%

Conditions

Temperature
70 °C

Procedure

Methyl hydroxyacetate (22 mg, 0.24 mmol) and 2-(5-(3-[(4-chloropyrimidin-2-yl)amino]-5-methylphenyl)-1,3-thiazol-2-yl)-1,1,1-trifluoropropan-2-ol (Example 98, 50 mg, 0.12 mmol) were taken up in N,N′-dimethylacetamide (1.2 mL). Cesium carbonate (118 mg, 0.36 mmol) was added and the mixture was stirred for 24 h at 70° C. The reaction was cooled to room temperature, quenched with saturated aqueous ammonium chloride, and extracted with ethyl acetate (2×). The combined organics were concentrated under reduced pressure and purified by reverse phase HPLC (10-80% acetonitrile/water+0.05% TFA modifier). Desired fractions were combined and lyophilized to afford {[2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}acetic acid (10 mg, 0.018 mmol, 15%) as the trifluoroacetic acid salt as a white solid. MS ESI: [M+H]+ m/z 455.1.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with saturated aqueous ammonium chloride
  3. extractionextracted with ethyl acetate (2×)
  4. concentrationThe combined organics were concentrated under reduced pressure
  5. custompurified by reverse phase HPLC (10-80% acetonitrile/water+0.05% TFA modifier)

Sources & evidence

ORD record
ord-8e57f43996de4c68862d44eb107ada68
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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